Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy

For the past few decades, the mechanisms of immune responses to cancer have been exploited extensively and significant attention has been given into utilizing the therapeutic potential of the immune system. Cancer immunotherapy has been established as a promising innovative treatment for many forms of cancer. Immunotherapy has gained its prominence through various strategies, including cancer vaccines, monoclonal antibodies (mAbs), adoptive T cell cancer therapy, and immune checkpoint therapy. However, the full potential of cancer immunotherapy is yet to be attained. Recent studies have identified the use of bioinformatics tools as a viable option to help transform the treatment paradigm of several tumors by providing a therapeutically efficient method of cataloging, predicting and selecting immunotherapeutic targets, which are known bottlenecks in the application of immunotherapy. Herein, we gave an insightful overview of the types of immunotherapy techniques used currently, their mechanisms of action, and discussed some bioinformatics tools and databases applied in the immunotherapy of cancer. This review also provides some future perspectives in the use of bioinformatics tools for immunotherapy.

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Cellular and Molecular Aspects of Anti-Melanoma Effect of Minocycline—A Study of Cytotoxicity and Apoptosis on Human Melanotic Melanoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21186917 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6917

Author(s):

Jakub Rok ◽

Zuzanna Rzepka ◽

Artur Beberok ◽

Justyna Pawlik ◽

Dorota Wrześniok

Keyword(s):

Myeloid Leukemia ◽

Standard Treatment ◽

Annexin V ◽

Medical Problem ◽

Melanoma Cells ◽

Carcinoma Cells ◽

Anti Cancer ◽

Acute Myeloid Leukemia Cells ◽

Molecular Aspects ◽

Therapy Result

Minocycline is a tetracycline compound with pleiotropic pharmacological properties. In addition to its antibacterial action, it shows many non-antimicrobial effects, including an anti-cancer activity. The anti-cancer action was confirmed in studies on ovarian carcinoma cells, hepatocellular carcinoma cells, glioma cells, or acute myeloid leukemia cells. Malignant melanoma remains a serious medical problem despite the extensive knowledge of the disease. The low effectiveness of the standard treatment, as well as the resistance to therapy, result in high mortality rates. This work aimed to investigate the potential and mechanisms of anti-melanoma action of minocycline. Human skin melanotic melanoma cell line COLO 829 was used in the study. The obtained results showed that minocycline decreased cell viability and inhibited the growth of melanoma cells, proportional to the drug concentration as well as to the time of incubation. The EC50 values were calculated to be 78.6 µM, 31.7 µM, and 13.9 µM for 24 h, 48 h, and 72 h, respectively. It was observed that treated cells had a disturbed cell cycle and significantly changed morphology. Moreover, minocycline caused a decrease in mitochondrial membrane potential and an increase in cells with a low level of reduced thiols. Finally, it was found that the anti-melanoma effect of minocycline was related to the induction of apoptosis. The drug activated caspases 8, 9, and 3/7 as well as increased the number of annexin V-positive cells. The presented results show that minocycline possesses anti-melanoma potential.

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P53 as a target for anti-cancer immunotherapy

Molecular Medicine Today ◽

10.1016/s1357-4310(97)01003-4 ◽

1997 ◽

Vol 3 (4) ◽

pp. 160-167 ◽

Cited By ~ 21

Author(s):

Hailei L. Chen ◽

David P. Carbone

Keyword(s):

Cancer Immunotherapy ◽

Anti Cancer

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Autoimmune Responses in Oncology: Causes and Significance

International Journal of Molecular Sciences ◽

10.3390/ijms22158030 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8030

Author(s):

Halin Bareke ◽

Pablo Juanes-Velasco ◽

Alicia Landeira-Viñuela ◽

Angela-Patricia Hernandez ◽

Juan Jesús Cruz ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Protein Microarrays ◽

Cross Reactivity ◽

Fine Tuning ◽

Cancer Treatments ◽

Aberrant Expression ◽

Specificity And Sensitivity ◽

Anti Cancer ◽

Life Threatening ◽

Considerable Impact

Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors. Understanding these responses has implications for both basic and clinical immunology. Autoantibodies in solid cancers can be used for early detection of cancer as well as for biomarkers of prognosis and treatment response. High-throughput techniques such as protein microarrays make parallel detection of multiple autoantibodies for increased specificity and sensitivity feasible, affordable, and quick. Cancer immunotherapy has revolutionized cancer treatments and has made a considerable impact on reducing cancer-associated morbidity and mortality. However, immunotherapeutic interventions such as immune checkpoint inhibition can induce immune-related toxicities, which can even be life-threatening. Uncovering the reasons for treatment-induced autoimmunity can lead to fine-tuning of cancer immunotherapy approaches to evade toxic events while inducing an effective anti-tumor immune response.

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Development of Small-Molecule STING Activators for Cancer Immunotherapy

Biomedicines ◽

10.3390/biomedicines10010033 ◽

2021 ◽

Vol 10 (1) ◽

pp. 33

Author(s):

Hee Ra Jung ◽

Seongman Jo ◽

Min Jae Jeon ◽

Hyelim Lee ◽

Yeonjeong Chu ◽

...

Keyword(s):

Cancer Immunotherapy ◽

Cyclic Gmp ◽

Therapeutic Potential ◽

Interferon Response ◽

Type I ◽

Anti Cancer ◽

Cancer Agent ◽

Sting Pathway

In cancer immunotherapy, the cyclic GMP–AMP synthase–stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from ‘cold’ to ‘hot’ through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.

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